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PubMed1998

A decision analysis of mandatory compared with voluntary HIV testing in pregnant women.

BACKGROUND: The benefit of antiretroviral therapy in reducing maternal-fetal transmission of HIV during pregnancy has caused a public policy debate about the relative benefits of mandatory HIV screening and voluntary HIV screening in pregnant women. OBJECTIVE: To evaluate the benefits and risks of mandatory compared with voluntary HIV testing of pregnant women to help guide research and policy. DESIGN: A decision analysis that incorporated the following variables: acceptance and benefit of prenatal care, acceptance and benefit of zidovudine therapy in HIV-infected women, prevalence of HIV infection, and mandatory compared with voluntary HIV testing. MEASUREMENTS: The threshold deterrence rate (defined as the percentage of women who, if deterred from seeking prenatal care because of a mandatory HIV testing policy, would offset the benefit of zidovudine in reducing vertical HIV transmission) and the difference between a policy of mandatory testing and a policy of voluntary testing in the absolute number of HIV-infected infants or dead infants. RESULTS: Voluntary HIV testing was preferred over a broad range of values in the model. At baseline, the threshold deterrence rate was 0.4%. At a deterrence rate of 0.5%, the number of infants (n = 167) spared HIV infection annually in the United States under a mandatory HIV testing policy would be lower than the number of perinatal deaths (n = 189) caused by lack of prenatal care. CONCLUSIONS: The most important variables in the model were voluntary HIV testing, the deterrence rate associated with mandatory testing compared with voluntary testing, and the prevalence of HIV infection in women of child-bearing age. At high levels of acceptance of voluntary HIV testing, the benefits of a policy of mandatory testing are minimal and may create the potential harms of avoiding prenatal care to avoid mandatory testing.

Anti-HIV Agents↗

PubMed2002

"Living" under the challenge of information decay: the stochastic corrector model vs. hypercycles.

The combined problem of having a large genome size when the accuracy of replication was a limiting factor is probably the most difficult transition to explain at the late stages of RNA world. One solution has been to suggest the existence of a cyclically coupled system of autocatalytic and cross-catalytic molecular mutualists, where each member helps the following member and receives help from the preceding one (i.e., a "hypercycle"). However, such a system is evolutionarily unstable when mutations are taken into account because it lacks individuality. In time, the cooperating networks of genes should have been encapsulated in a cell-like structure. But once the cell was invented, it closely aligned genes' common interests and helped to reduce gene selfishness, so there was no need for hypercycles. A simple package of competing genes, described by the "stochastic corrector model" (SCM), could have provided the solution. Until now, there is no clear demonstration that the proposed mechanisms (compartmentalized hypercycles and the stochastic corrector model) do in fact solve the error threshold problem. Here, we present a Monte Carlo model to test the viability of protocell populations that enclose a hypercyclic (HPC) or a non-hypercyclic (SCM) system when faced with realistic mutation rates before the evolution of efficient enzymic machinery for replication. The numerical results indicate that both systems are efficient information integrators and are able to overcome the danger of information decay in the absence of accurate replication. However, a population of SCM protocells can tolerate higher deleterious mutation rates and reaches an equilibrium mutational load lower than that in a population of HPC protocells.

Animals↗

PubMed1980

Integral equation models for endemic infectious diseases.

Endemic infectious diseases for which infection confers permanent immunity are described by a system of nonlinear Volterra integral equations of convolution type. These constant-parameter models include vital dynamics (birth and deaths), immunization and distributed infectious period. The models are shown to be well posed, the threshold criteria are determined and the asymptotic behavior is analysed. It is concluded that distributed delays do not change the thresholds and the asymptotic behaviors of the models.

Communicable Diseases↗

PubMed1992

Spatial localization without visual references.

To explain the veridical percept of the spatial ordering of objects and the generation of eye movements to peripheral targets, Lotze (1885 Microcosmos. Edinburgh: T. & T. Clark) proposed that there is a position label (local sign) for each retinal element. To estimate the precision of local sign information, we measured absolute localization thresholds at various eccentricities in the nasal visual field, in the complete absence of visual references. To eliminate perception of the visual surround, observers viewed a large display screen through a neutral density filter (2.0 log unit) in a dark room. The fixation target was extinguished at various times (interstimulus intervals or ISIs) prior to the onset of the test stimulus. In general, our results show that localization thresholds are proportional to the target eccentricity at all ISIs. At each eccentricity, localization thresholds are elevated after the extinction of the visual reference compared to thresholds when the reference is present. However, relative to the referenced threshold, unreferenced thresholds are elevated by a greater proportion at smaller eccentricities than at larger eccentricities. Our threshold vs ISI data can be adequately modeled on the basis of an intrinsic positional uncertainty, which increases with eccentricity, and additive and multiplicative sources of noise. The additive noise appears to reflect primarily the increasing scatter in eye position when the fixation target is extinguished. Our model's estimate of intrinsic positional uncertainty in the isoeccentric direction appears to reflect primarily the intrinsic positional uncertainty of the peripheral retina (the local sign), being very similar to cumulative cone position uncertainty and to the spacing between ON-P beta ganglion cells. In the isoeccentric direction, the estimated precision of the local sign mechanism across eccentricities is slightly better than the precision of saccadic endpoints, suggesting that noise in the motor system must also contribute to the scatter of saccadic endpoints in the isoeccentric direction. Interestingly, in the radial direction, we find a surprising similarity in our observers' positional uncertainty and the precision of saccadic endpoints.

Fovea Centralis↗

PubMed1998

Pubic arch detection in transrectal ultrasound guided prostate cancer therapy.

New biopsy techniques, increased life expectancy, and prostate-specific antigen (PSA) screening have contributed to an increase in the reported incidence of prostate cancer. Among several treatment options available to the patients, transperineal prostate brachytherapy has emerged as a medically successful, cost-effective outpatient procedure for treating localized prostate cancer. Transperineal prostate brachytherapy employs transrectal ultrasound (TRUS) as the primary imaging modality to accurately preplan and subsequently execute the placement of radioactive seeds into the prostate. Under TRUS guidance, a needle (preloaded with radioactive seeds) is inserted through a template guide, through the perineum and into a predetermined prostate target. The pubic arch, formed by the central union of pelvic bones, is a potential barrier to the passage of these needles in the prostate. A critical aspect, therefore, in the planning and execution of the brachytherapy procedure is the accurate assessment of pubic arch interference (PAI) in relation to the prostate. Traditionally, the evaluation of PAI has involved computed tomography correlate scanning or crude subjective evaluations. In this paper, we describe a new method of assessing PAI by detecting the pubic arch via image processing on the TRUS images. The PAI detection (PAID) algorithm first uses a technique known as sticks to selectively enhance the contrast of linear features in ultrasound images. Next, the enhanced image is thresholded via percentile thresholding. Finally, we fit a parabola (a model for the pubic arch) recursively to the thresholded image. Our evaluation result from 15 cases indicates that the algorithm can successfully detect the pubic arch with 90% accuracy. Based on this study, we believe that detecting the pubic arch and assessing PAI can be done practically and more accurately in the clinical setting using TRUS rather than the current available methods.

Brachytherapy↗

PubMed2005

A cost minimization model for the treatment of minor bleeding episodes in patients with haemophilia A and high-titre inhibitors.

Treatment of acute bleeding episodes in patients with haemophilia A and inhibitory antibodies to factor VIII (FVIII) most often involves the use of bypassing haemostatic agents, such as activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa). We constructed a cost minimization model to compare the costs of initial treatment with aPCC vs. rFVIIa in the home treatment of minor bleeding episodes. We developed a clinical scenario describing such a case and presented it to a panel of US haemophilia specialists. For each product class, we asked panellists to provide dosing regimens required to achieve complete resolution of a minor haemarthrosis in a child with high-titre inhibitors, and for the probabilities of success at two time points (8-12 and 24 h). Consensus among the panellists was refined by a second round of the process, and the median values resulting were used as inputs to a decision analysis model. Sensitivity analyses were conducted to determine threshold values for key variables. The base case model found that initial treatment with aPCC would result in a mean cost per episode of 21 000 dollars, compared with 33 400 dollars for initial treatment with rFVIIa. Sensitivity analyses over a range of clinically plausible values for cost, dosing, and efficacy did not change the selection of aPCC as the dominant strategy.

Autoantibodies↗

PubMed1978

Hearing threshold for a decaying oscillatory waveform.

Hearing thresholds for a damped wave signal are measured at 8 frequencies from .35 -- 4 kc/s, and compared with hearing thresholds for pure-tone signals of the same frequencies. Hearing threshold for a damped wave signal is expressed in peak db re 20 uPa. Differences range somewhat irregularly from 8.6 to 19.6 db in favor of pure-tone signals. The difference between both threshold levels is described by a simple model.

Adolescent↗

PubMed2003

Frequency dependence of the cardiac threshold to alternating current between 10 Hz and 160 Hz.

It is still unclear what fundamental criteria influence the ability of alternating current (AC) to induce ventricular fibrillation (VF) in vivo. As the VF threshold has a bowl-shaped relationship with frequency (showing a minimum threshold at some frequency), similar to the nervous system, one proposed model has assumed that the mechanisms underlying AC stimulation of nerves are at work for VF induction. More recent work has suggested a second approach, whereby a simple RC-like model is sufficient to understand the cardiac AC stimulation threshold's frequency dependence, suggesting that some unarticulated mechanism is at work for VF. The paper directly tests these two models. In 12 intact dogs and 20 intact guinea pigs, DC pulses were used to stimulate AC square and AC sine waves at 10, 20, 40, 80 and 160 Hz. All electrodes were endocardial, with the return electrode being on a paw or thorax. It was found that, for square and sine wave stimulation in both dogs and guinea pigs, the stimulation threshold increased monotonically with frequency from 10 Hz up to 160 Hz (p < 0.01 for dogs and guinea pigs). Between 80 and 160 Hz, the AC stimulation threshold doubled, exactly as predicted by an RC model. It was concluded that the AC stimulation threshold is not bowl-shaped and is best understood with an RC model. As the VF threshold does exhibit a bowl-shape with frequency, as opposed to the stimulation threshold which does not, the VF induction frequency dependence must have different origins.

Animals↗

PubMed1999

Persistence of tick-borne virus in the presence of multiple host species: tick reservoirs and parasite mediated competition.

Tick-borne viruses in tropical and temperate parts of the world have a significant impact on human, livestock and wildlife hosts both directly, through mortality/morbidity, and economically. Since the ticks have multiple life stages and can utilize a large range of host species our understanding of the dynamics of these infections is often not clear. In this paper we consider the impact of a population which is a tick host but non-viraemic on one which is both a tick host and viraemic. We present two simple deterministic models and use joint threshold density curves to illustrate the basic reproductive ratios of both the ticks and the virus. We find that the non-viraemic hosts can have considerable impact on the viraemic host. Either they amplify the tick population and cause the virus to persist, or they dilute the infection and cause it to die out. A general model framework is presented here but a special case of this model describes the red grouse-hare-Louping-ill system.

Animals↗

PubMed2003

Metabolic presbycusis: differential changes in auditory brainstem and otoacoustic emission responses with chronic furosemide application in the gerbil.

Auditory characteristics of metabolic or strial presbycusis were investigated using an animal model in which young adult Mongolian gerbils ( Meriones unguiculates) were implanted with an osmotic pump supplying furosemide continuously to the round window. This model causes chronic lowering of the endocochlear potential (EP) and results in auditory responses very similar to those seen in quiet-aged gerbils (Schmiedt et al., J. Neurosci. 22:9643-9650, 2002). Auditory function was examined up to one week post-implant by measurement of auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). Emission "threshold" was defined as the stimulus level required to reach a criterion emission amplitude. Comparing all responses on a "threshold-shift diagram," where emission threshold increases were plotted versus ABR threshold increases, the following results were obtained: (1) On average, the increase of the emission threshold was about 55% of the increase in ABR threshold, with comparatively little scatter. (2) The main dysfunction in metabolic presbycusis appears to be a decrease in the gain of the cochlear amplifier, combined with an additional, smaller increase in neural threshold, both effects caused by a chronically low EP. (3) For ABR threshold increases over 20 dB, the points for the chronic low-EP condition were largely separate from those previously found for permanent acoustic damage. The threshold-shift diagram therefore provides a method for noninvasive differential diagnosis of two common hearing dysfunctions.

Animals↗

PubMed2002

A risk-factor model of epistatic interaction, focusing on autism.

Research to date on the genetics of autism has not uncovered a major susceptibility locus and indications are that a number of genes, perhaps as many as 15-20, may play detectable but minor roles in the etiology of the condition. To cope with this situation, a risk-factor model based on standard epidemiologic designs is proposed. The model supposes that adding a factor to a fixed set of existing factors always increases the total risk. Thus, according to the model genetic contributions cumulate but are not necessarily additive. A threshold, hence, epistasis is required. The model is applied to several conditions in which the risk of autism is elevated, some genetic (fragile X, tuberous sclerosis) and some exogenous (rubella and thalidomide embryopathies). Male gender is discussed as a risk factor. This approach is contrasted primarily with Gillberg and Coleman's view of autism as "a syndrome or series of syndromes caused by many different separate individual diseases." The principal point of difference is whether the effects of different causes cumulate or do not cumulate. In the present approach they do, in Gillberg and Coleman's they do not.

Autistic Disorder↗

PubMed1983

Intracortical processing of visual contour information in cats.

Fine slices made through the gray matter perpendicular to the surface of cortical area 17-18 in the cat produced no change in behavioral measures of grating acuity, a modest reduction in vernier acuity and a proportionately larger effect on contour orientation acuity. The introduction of vertical gaps in the vernier acuity targets produced increases in the vernier offset threshold proportional to the gap size both before and after cortical damage, except at the largest vertical gap values employed (1-1.5 degrees) where no change in thresholds was observed after surgery. Neither the preoperative vernier thresholds nor the postoperative changes in vernier thresholds were predicted by the measured contour orientation thresholds and thus an orientation discrimination model of vernier acuity was not supported. The results of this study support the view that intracortical processing in area 17-18 is important in both vernier and orientation acuity, but the neural mechanisms mediating the two capacities are different.

Animals↗

PubMed2006

Modeling the HIV/AIDS epidemic among injecting drug users and sex workers in Kunming, China.

This paper presents a mathematical model of the HIV/AIDS epidemic in Kunming, the provincial capital of Yunnan, China. The population is divided into several groups, with individuals possibly changing group. Two transmission routes of HIV are considered: needle sharing between injecting drug users (IDUs) and commercial sex between female sex worker (FSWs) and clients. The model includes male IDUs who are also clients and female IDUs who are also FSWs. Groups are split in two--risky and safe--according to condom use and needle sharing. A system of partial differential equations is derived to describe the spread of the disease. For the simulation, parameters are chosen to fit as much as possible data publicly available for Kunming. Some mathematical properties of the model--in particular the epidemic threshold R0 which determines the goal of public health interventions--are also presented. Though the model couples two transmission routes of HIV, the approximation R0 approximately = max[R0(IDU), R0(sex)], with closed formulas for R0(IDU) and R0(sex), appears to be quite good. The critical levels of condom use and clean needle use necessary to stop both the sexual transmission and the transmission among IDUs can therefore be determined independently.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Dynamic population epidemic models.

Most multipopulation epidemic models are of the contact distribution type, in which the locations of successive contacts are chosen independently from appropriate contact distributions. This paper is concerned with an alternative class of models, termed dynamic population epidemic models, in which infectives move among the populations and can infect only within their current population. Both the stochastic and deterministic versions of such models are considered. Their threshold behavior is analyzed in some depth, as are their final outcomes. Velocities of spread of infection are considered when the populations have a spatial structure. A criterion for finding the equivalent contact distribution epidemic for any given dynamic population epidemic is provided, enabling comparisons to be made for the velocities and final outcomes displayed by the two classes of models. The relationship between deterministic and stochastic epidemic models is also discussed briefly.

Disease Outbreaks↗

PubMed2005

Simulations of motor unit number estimation techniques.

Motor unit number estimation (MUNE) is an electrodiagnostic procedure used to evaluate the number of motor axons connected to a muscle. All MUNE techniques rely on assumptions that must be fulfilled to produce a valid estimate. As there is no gold standard to compare the MUNE techniques against, we have developed a model of the relevant neuromuscular physiology and have used this model to simulate various MUNE techniques. The model allows for a quantitative analysis of candidate MUNE techniques that will hopefully contribute to consensus regarding a standard procedure for performing MUNE.

Action Potentials↗

PubMed2005

Statistical physics models for nacre fracture simulation.

Natural biological materials such as nacre (or mother-of-pearl), exhibit phenomenal fracture strength and toughness properties despite the brittle nature of their constituents. For example, nacre's work of fracture is three orders of magnitude greater than that of a single crystal of its constituent mineral. This study investigates the fracture properties of nacre using a simple discrete lattice model based on continuous damage random thresholds fuse network. The discrete lattice topology of the proposed model is based on nacre's unique brick and mortar microarchitecture, and the mechanical behavior of each of the bonds in the discrete lattice model is governed by the characteristic modular damage evolution of the organic matrix that includes the mineral bridges between the aragonite platelets. The analysis indicates that the excellent fracture properties of nacre are a result of their unique microarchitecture, repeated unfolding of protein molecules (modular damage evolution) in the organic polymer, and the presence of fiber bundle of mineral bridges between the aragonite platelets. The numerical results obtained using this simple discrete lattice model are in excellent agreement with the previously obtained experimental results, such as nacre's stiffness, tensile strength, and work of fracture.

Animals↗

PubMed2005

Visible-near infrared reflectance spectroscopy for rapid, nondestructive assessment of wetland soil quality.

Recent evidence supports using visible-near infrared reflectance spectroscopy (VNIRS) for sensing soil quality; advantages include low-cost, nondestructive, rapid analysis that retains high analytical accuracy for numerous soil performance measures. Research has primarily targeted agricultural applications (precision agriculture, performance diagnostics), but implications for assessing ecological systems are equally significant. Our objective was to extend chemometrics for sensing soil quality to wetlands. Hydric soils posed two challenges. First, wetland soils exhibit a wider range of organic matter concentrations, particularly in riparian areas where levels range from <1% in sedimentation zones to >90% in backwater floodplains; this may mute spectral responses from other soil fractions. Second, spectral inference of cation concentrations in terrestrial soils is for oxidized species; under reducing conditions in wetlands, oxidation state variability is observed, which strongly affects chroma. Riparian soils (n = 273) from western Florida exhibiting substantial target parameter variability were compiled. After minimal pre-processing, soils were scanned under artificial illumination using a laboratory spectrometer. A multivariate data mining technique (regression trees) was used to relate post-processed reflectance spectra to laboratory observations (pH, organic content, cation concentrations, total N, C, and P, extracellular enzyme activity). High validation accuracy was generally observed (r2(validation) > 0.8, RPD > 2.0, where RPD is the ratio of the standard deviation of an attribute to the observed standard error of validation); where accuracy was lower, categorical models (classification trees) successfully screened samples based on diagnostic functional thresholds (validation odds ratio > 10). Graphical models verified significant association between predictions and observations for all parameters, conditioning on biogeochemical covariates. Visible-near infrared reflectance spectroscopy offers both cost and statistical power advantages; hydric conditions do not appear to constrain application.

Cost Control↗

PubMed1995

Perceived motion of contrast-modulated gratings: predictions of the multi-channel gradient model and the role of full-wave rectification.

The paper examines the perception of motion in contrast-modulated sine-wave grating patterns. These non-rigid motion patterns give rise to a spatially-structured motion percept in which perceived speed varies with spatial position. We measured the perceived motion of the low contrast regions of amplitude-modulated gratings as a function of the carrier frequency, the carrier speed, the shape of the modulation signal and the modulation depth. We found that for static carriers perceived speed was greatest in the low contrast regions of the display. The speed of the low contrast regions was underestimated and perceived speed decreased as the spatial frequency of the carrier increased. When the direction of the motion of the carrier was opposite to that of the contrast modulation, the low contrast regions could appear to be stationary. The perceived speed of the contrast modulation increased with modulation depth. The brightness contrast of the carrier grating had little effect on perceived speed of contrast-modulated patterns for average contrasts of over 10%. A motion model which had full-wave rectification as an explicit pre-processing stage followed by low-pass filtering or some other selection criterion, would predict that the motion of contrast-modulated gratings should appear rigid and that the motion of the envelope should be judged correctly. The Multi-channel Gradient Model however predicts both the structured motion field experienced when viewing these second-order motion patterns and the reductions in perceived speed as a function of carrier spatial frequency and carrier speed.

Contrast Sensitivity↗